We discovered that 1 microgram/ml gp120 rapidly and completely blocks the pharmacologically isolated, voltage-activated calcium current in voltage- clamped rat pituitary tumor cells (GH4C1), an effect that is prevented by preincubation with an excess of CD4 protein from lymphocytes. This result is exactly opposite to earlier reports with indirect methods. By comparison the same concentration of gp120 had no effect whatsoever on the voltage-activated outward currents through potassium selective ion channels in GH4C1 cells. In immortalized mouse hypothalamaic neurons, GP120 did stimulate pharmacologically isolated calcium current. However, this result was demonstrated to be a pharmacological effect of micromolar sodium ions in the buffer added with GP120. Because central neurons often express tetrodotoxin-resistant sodium channels, calcium currents are often measured in 0 Na+, which might explain previous reports of calcium current stimulation by GP120.